Interactions between cancer cells and host tissues play an important role in determining the clinical course of cancer. It is not known how cells in an organism distinguish self from non-self and react appropriately, but it is probable that a breakdown in this recognition process occurs in the change from normal to malignant state and in the spread of cancer by metastasis or invasion throughout the body. We have already shown that the aggregation of embryonic neural retina cells can serve as a sensitive model system for investigation of cellular recognition in normal-normal and normal cell-cancer cell interactions through use of the specific inhibiting effects of mouse cancer cells compared to "normal" cells. One objective of the project is to study the effects on this inhibition of modifiers of cell surface properties, surface enzymes and cellular metabolism in an attempt to elucidate the mechanism of the inhibition. Another objective is to assess the generality of our basic observations by testing a number of different cell types of cancer and non-malignant origin. Particular emphasis will be put on studies of human cells in this part of the project. Our technique involves observing the effects of small numbers of "test" cells on the aggregative behavior of neural retina cells. The effects are assayed by direct measurements of neural retina aggregate size, number of aggregates and the rate of loss of single neural retina cells into aggregates. Autoradiographic and radioisotopic counting techniques will be used to determine the penetration of "test" cells into neural retina aggregates and stationary cultures will be employed to study the behavior of individual cells. The data from experiments involving aggregating cells will be used to guide experiments on the interaction of cancer cells with normal and cancer tissue fragments giving added relevance. The results obtained should give some further understanding of the differential effects of normal and cancer cells on other cell types and may indicate ways of altering cancer cell behavior in vivo.